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dc.contributor.authorLemkul, Justin A.
dc.description.abstractDNA and RNA sequences rich in guanine can fold into noncanonical structures called G-quadruplexes (GQs), which exhibit a common stem structure of Hoogsteen hydrogen-bonded guanine tetrads and diverse loop structures. GQ sequence motifs are overrepresented in promoters, origins of replication, telomeres, and untranslated regions in mRNA, suggesting roles in modulating gene expression and preserving genomic integrity. Given these roles and unique aspects of different structures, GQs are attractive targets for drug design, but greater insight into GQ folding pathways and the interactions stabilizing them is required. Here, we performed molecular dynamics simulations to study two bimolecular GQs, a telomeric DNA GQ and the analogous telomeric repeat-containing RNA (TERRA) GQ. We applied the Drude polarizable force field, which we show outperforms the additive CHARMM36 force field in both ion retention and maintenance of the GQ folds. The polarizable simulations reveal that the GQs bind bulk K+ ions differently, and that the TERRA GQ accumulates more K+ ions, suggesting different ion interactions stabilize these structures. Nucleobase dipole moments vary as a function of position and also contribute to ion binding. Finally, we show that the TERRA GQ is more sensitive than the telomeric DNA GQ to water-mediated modulation of ioninduced dipole-dipole interactions.en
dc.description.sponsorshipNational Institutes of Health [R35GM133754]; Thomas F. and Kate Miller Jeffress Memorial Trust (Bank of America, Trustee), USDA-NIFA [VA-160092]; Virginia Tech Office of the Provost, College of Agriculture and Life Sciences, and Department of Biochemistry; Computing time and resources were provided by Virginia Tech Advanced Research Computing. Funding for open access charge: NIGMS [R35GM133754] and the Thomas F. and Kate Miller Jeffress Memorial Trust.en
dc.publisherOxford University Pressen
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.titleSame fold, different properties: polarizable molecular dynamics simulations of telomeric and TERRA G-quadruplexesen
dc.typeArticle - Refereeden
dc.title.serialNucleic Acids Researchen

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Creative Commons Attribution-NonCommercial 4.0 International
License: Creative Commons Attribution-NonCommercial 4.0 International